Genetics in Medicine (2025) 27, 101453 www.journals.elsevier.com/genetics-in-medicine ARTICLE Psychological and emotional impacts of communicating breast cancer risk using multifactorial assessment with polygenic risk score: Findings from PERSPECTIVE I&I Laurence Lambert-Côté1 , Annie Turgeon1, Kristina M. Blackmore2, Amy Chang2, Antonis C. Antoniou3, Kathleen A. Bell2, Mireille J.M. Broeders4, Jennifer D. Brooks5, Tim Carver3, Sue-Ling Chang1, Jocelyne Chiquette1,6,7, Éric Demers1, Douglas F. Easton3, Andrea Eisen2,8, Laurence Eloy9,10, D. Gareth R. Evans11, Samantha Fienberg2, Yann Joly12, Raymond H. Kim2,13, Bartha M. Knoppers12, Corinne Labeau-Caouette1, Johanne Lessard10, Aisha Lofters14, Hermann Nabi1,15,16, Jean-Sébastien Paquette7, Nora Pashayan3, Amanda J. Sheppard2,5, Tracy L. Stockley13,17,18, Meghan J. Walker2,5, Anna M. Chiarelli2,5, Jacques Simard1,19, Michel Dorval1,16,20,* A R T I C L E I N F O Article history: Received 26 November 2024 Received in revised form 23 April 2025 Accepted 23 April 2025 Available online 10 May 2025 Keywords: Breast cancer screening Polygenic risk score Psychosocial issues Risk communication Risk stratification The Article Publishing Charge (APC) for this Anna M. Chiarelli, Jacques Simard, and Mic *Correspondence and requests for materials Sainte-Foy, Quebec City, QC, Canada G1S 4L8. Affiliations are at the end of the document. doi: https://doi.org/10.1016/j.gim.2025.101453 1098-3600/© 2025 The Authors. Published by El under the CC BY-NC-ND license (http://creative A B S T R A C T Purpose: To examine the psychological and emotional outcomes of personalized breast cancer risk communication up to 1 year after disclosure in a risk-stratified breast screening preimplementation study (Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation). Methods: Among 3753 females aged 40 to 69, unaffected by breast cancer, with a prior mammogram, and who underwent multifactorial risk assessment to estimate their 10-year breast cancer risk, 2734 completed follow-up questionnaires up to 1 year after risk communication: 78.5% were at average risk, 16.5% at higher than average risk, and 5.0% at high risk. The impact of risk communication on breast cancer worry and psychological distress and factors associated with decisional regret were examined. Results: Breast cancer worry and psychological distress scores remained low after risk communication and at 1 year follow-up. Up to 1 year after disclosure, small significant differences in breast cancer worry were observed between risk levels. Decisional regret was very low 1 year after risk communication. Lower levels of decisional regret were significantly associated with some factors, including higher satisfaction with the information received. Conclusion: This study suggests that personalized breast cancer risk communication has low negative psychological and emotional effects and highlights the importance of the information received for implementing this approach at population level. article was paid through institutional agreement with Université Laval. hel Dorval contributed equally to this work. should be addressed to Michel Dorval, CHU de Québec-Université Laval Research Center, 1050 chemin Email address: michel.dorval@crchudequebec.ulaval.ca sevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article commons.org/licenses/by-nc-nd/4.0/). Delta:1_given-name https://orcid.org/0000-0003-2598-7094 Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname Delta:1_given-name Delta:1_surname https://orcid.org/0000-0002-3207-8211 mailto:michel.dorval@crchudequebec.ulaval.ca http://crossmark.crossref.org/dialog/?doi=10.1016/j.gim.2025.101453&domain=pdf http://www.journals.elsevier.com/genetics-in-medicine https://doi.org/10.1016/j.gim.2025.101453 http://creativecommons.org/licenses/by-nc-nd/4.0/ 2 L. Lambert-Côté et al. © 2025 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Introduction Population-based breast screening programs have been implemented in many countries and have been associated with significant reductions in breast cancer mortality.1 Risk- stratified breast cancer screening using multifactorial risk assessment, including a polygenic risk score (PRS), is increasingly regarded as an alternative to the current age- based screening.2-6 This approach has the potential to improve the benefit-to-harm ratio and the cost-effectiveness of screening programs by tailoring screening recommenda- tions to individual risk.7,8 Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integra- tion and Implementation (PERSPECTIVE I&I) is an ongoing Canadian project that seeks to improve personal- ized risk assessment, to inform the development of cost- effective risk-based approaches for prevention and early detection of breast cancer, and to determine optimal implementation approaches within the Canadian health care system.5,9 Various issues need to be considered when implementing a personalized risk-based breast cancer screening at the population level.5,6 An important consideration is the po- tential negative impacts of risk assessment and communi- cation on individuals. Current literature on monogenic (eg, BRCA) and polygenic testing (eg, PRS) in cancer genetic clinic settings indicates no evidence of clinically significant long-term adverse psychological outcomes or substantial decisional regret.10,11 In contrast, population-level multi- factorial risk assessment adds complexity by encompassing multiple risk factors, which requires a more nuanced inter- pretation of risk. This complexity may contribute to increased uncertainty or anxiety because it underscores the intricate interplay of lifestyle, environmental, and genetic factors in determining risk and potentially overwhelming individuals with respect to the actions they can take to mitigate it. Consequently, the psychological impacts of risk communication derived from previous studies on mono- genic or polygenic testing may not be directly applicable to multifactorial risk evaluations. Previous studies in the United States12 and England13,14 have evaluated the psychological impact of providing women with breast cancer risk estimates using multifactorial risk assessment. These studies have shown that personalized breast cancer risk communication has a modest impact on breast cancer worry and anxiety and is unlikely to have adverse consequences in this respect.12-14 Of these, only the Predicting-Risk-Of-Cancer-At-Screening (PROCAS-2) study (Breast Cancer Predict) involved women with different levels of risk (high, moderate, average, and below average) but included only a highly selected subsample of the study population.14 The studies only followed par- ticipants for up to 6 months; therefore, they did not provide a longer-term perspective. Additionally, they did not mea- sure decisional regret, which is important to consider when implementing a risk-based screening approach in existing screening programs because it could affect future engagement. This study evaluated the psychological and emotional outcomes of breast cancer risk communication up to 1 year after disclosure in a real-word setting using the PERSPECTIVE I&I prospective cohort study. The study aimed to test the hypothesis that women identified as high risk would experience higher levels of breast cancer worry and psychological distress compared with those at average risk in the short term, with no clinically significant differ- ences anticipated between the groups after 1 year. It also explored which factors, beyond risk levels, are associated with higher decisional regret 1 year after risk communica- tion. Finally, it explored the emotional dimension of learning about breast cancer risk level 1 year after risk disclosure. Materials and Methods Context This research was conducted as part of the Canadian PERSPECTIVE I&I project fully described elsewhere.5,9 Briefly, participants completed an entry questionnaire that inquired about their family history of cancer, as well as lifestyle and hormonal risk factors. Participants also pro- vided a saliva sample from which DNA was extracted and tested to calculate a PRS with 295 single nucleotide poly- morphisms (SNPs) based on the 313-SNP breast cancer PRS previously identified.15,16 Participants were not screened for pathogenic variants in monogenic cancer susceptibility genes (eg, BRCA1, BRCA2, PALB2, CHEK2, and ATM). Mammographic density was obtained from the screening mammogram report. The 10-year absolute risk of having breast cancer was calculated using the multifactorial Can- Risk prediction tool, which integrates all collected risk factors, including family history, PRS, lifestyle and hor- monal factors, and breast density.17 Risk estimates were stratified into 3 categories using age-dependent absolute risk thresholds: average (<15%,), higher than average (15 to <25%), and high (≥25%), which correspond to a breast cancer remaining lifetime risk from ages 30 to 80 years.18 The PRS and the risk assessment tool (CanRisk) were pri- marily developed using individuals of European ancestry, which resulted in less accurate performance across all http://creativecommons.org/licenses/by-nc-nd/4.0/ L. Lambert-Côté et al. 3 ethnicities. For ethical reasons and to ensure equity, we did not exclude participants based on ethnicity. Instead, we included a disclaimer in the consent form, noting that the risk estimate provided might be less precise for certain groups. All participants received a personalized risk letter that included their risk level and proposed screening action plan. This document was accessible via a secured web portal or sent by mail. Screening action plans were based on risk level, age and provincial breast screening guidelines (Supplemental Table 1).5 For women aged 40 to 49 who are estimated to be at average risk, no mammography screening is recommended, whereas women aged 50 to 69 should be screened every 2 years by mammography. Women esti- mated to be at higher-than-average risk (40-69 years) in Quebec are recommended to undergo screening every 1 to 2 years, whereas in Ontario, they are encouraged to discuss screening options with their primary care provider (40-49 years) or undergo annual screening with mammogram (50- 69 years). Finally, it is proposed that all women (40-69 years) estimated to be at high risk undergo annual screening with both a mammogram and magnetic resonance imaging. Women identified as high risk were contacted by a health care professional (nurse or genetic counselor) to disclose their risk level and/or for further counseling about their risk level and screening action plan. The study was approved by the Ethics Research Com- mittees of the CHU de Québec-Université Laval (MP-20- 2020-4670), McGill University (A12-B65-18A), University of Toronto (00036881), Grand River Hospital (2020-0709), McMaster University (11468), St. Michael’s Hospital (19- 220), Sunnybrook Health Sciences Centre (2255), Univer- sity Health Network (19-5340), and Queens University (6030732 EPID-712-20). Informed consent was obtained from all participants involved in the study. Participants The PERSPECTIVE I&I project recruited females aged 40 to 69 years who had at least 1 previous mammogram. Those who had been diagnosed with breast, ovarian, or pancreatic cancer, had a mastectomy, had genetic counseling and/or genetic testing for breast cancer, or had received chest radiotherapy treatments before the age of 30 were ineligible. For this study, participants from the PERSPECTIVE I&I cohort who had a risk calculated and communicated to them and who completed all 3 questionnaires were included. Participants were excluded if they reported a breast cancer diagnosis in 1 of the follow-up questionnaires. Data collection Data from the 3 questionnaires were used: (1) the entry questionnaire (before risk assessment: July 2019-December 2021); (2) the follow-up questionnaire (at the time of risk communication: March 2020-October 2022); and (3) the 1-year follow-up questionnaire (1 year after risk communication: April 2021-August 2023). The question- naires were administered in both English (Ontario) and French (Quebec). Measures Questions used to measure the emotional outcome of knowing their risk level, breast cancer worry, psychological distress, and decisional regret are shown in Supplemental Questionnaire 1. Breast cancer worry Breast cancer worry was assessed using 5 questions adapted from the Lerman Breast Cancer Worry Scale19 used in previous studies.12,20 Participants were asked about how often in the past month they had any thoughts, worries, or feelings of distress about their risk of developing breast cancer and how often their thoughts affected their mood and daily activities. The breast cancer worry score ranged from 5 to 20, a higher score indicating more frequent thoughts or greater worry about breast cancer risk. Data from all 3 questionnaires were used for this analysis. Psychological distress Psychological distress was assessed using the Kessler Psy- chological Distress Scale (K10), which consists of 10 questions about emotional states experienced in the past 30 days.21,22 The psychological distress score ranged from 0 to 40, a higher score indicating a higher level of psychological distress. Data from all 3 questionnaires were used for this analysis. Regret after the decision to know the level of risk Regret after the decision to know the level of risk was assessed using the decision regret scale,23 a validated 5-item scale with scores ranging from 0 to 100. A score of 0 indi- cated no regret, whereas a score of 100 meant great deci- sional regret. Data from the 1-year follow-up questionnaire were used for this analysis. Information on follow-up with the health care providers, the intention to follow the screening action plan, and satisfaction with the information received Information on follow-up with the health care providers (HCPs), the intention to follow the screening action plan, and satisfaction with the information received was also collected 1 year after risk communication. Participants were asked if they had discussed their risk level with their HCP. If they had, shared decision making on the proposed screening action plan was measured from the participant’s perspective using 4 items from the Shared Decision-Making Question- naire.24 Each item was measured using a 5-point scale with scores ranging from 4 to 20. The participants also indicated 4 L. Lambert-Côté et al. if they had chosen to follow the proposed screening action plan. Satisfaction with the information received was assessed using an adaptation of a previously published scale.14,25 The satisfaction score ranged from 5 to 20, with higher scores indicating higher satisfaction. All of these questions are shown in Supplemental Questionnaire 2. Emotional outcomes of knowing risk level Emotional outcomes of knowing risk level were assessed using 2 questions evaluating the extent to which learning their breast cancer risk level was a relief or was upsetting for them.26 Data from the 1-year follow-up questionnaire were used for this analysis. Sociodemographic and health information Sociodemographic and health information included the participant’s province and age group at risk assessment. Variables obtained from the entry questionnaire included the country of birth, ethnic or cultural origin, marital status, highest level of education, employment status, and perceived general health. These variable definitions were derived from Canadian census questionnaires. Using Sta- tistics Canada’s definition, we categorized individuals as visible or nonvisible minorities, based on their ethnic or cultural origins. Visible minorities, as defined by the Employment Equity Act, include groups such as South Asian, Chinese, Black, Filipino, Arab, Latin American, Southeast Asian, West Asian, Korean, and Japanese.27 This definition was used to align with Canadian terminology at the time of the study and to ensure reliable, robust estimates, given that population groups other than White were rela- tively small in our sample.9 Other self-reported covariates included personal history of breast cancer, number of previous mammograms, age at first mammogram, mammogram screening frequency, and perceived lifetime breast cancer risk. Data analysis To evaluate the impact of risk communication on breast cancer worry and psychological distress, we used a general- ized linear model with an identity link and normal distribution and generalized estimating equations to account for correla- tion over time. Analyses were adjusted for potential con- founding variables (age group, province, education, visible minority status, family history of breast cancer, perceived risk, and worry about breast cancer). Province was considered as a potential confounding variable to account for different recruitment methods used in each province (recruitment through population-based invitations within the provincial screening program vs convenience sampling). These methods resulted in variations in age groups, sociodemographic, risk factors, and risk level distribution, as previously reported.9 Participants with missing values for at least 1 of the 3 mea- surement points or adjustment variables were excluded from the analyses. To assess factors associated with decisional regret 1 year after risk communication, we computed adjusted mean scores and 95% confidence intervals using a general- ized linear model with a log link and a Poisson working model in univariable and multivariable models.28 Model- robust variances were obtained with sandwich estimators to account for the larger variance of Poisson variables compared with binomial variables.29 A stepwise covariate selection method was used for the multivariable model. In addition, the following variables were systematically included in the multivariable model: age group at risk assessment (40-49, 50- 59, and 60-70), province, and the interaction term between the for risk levels and the family history. Additional information on data analysis is described in the Supplemental Data Analysis. Statistical analyses were performed using SAS software version 9.4 (SAS Institute Inc). Results Among the 4477 participants recruited in the PERSPEC- TIVE I&I project, 3714 had their risk level calculated and disclosed. All 3 questionnaires were sent to 3672 participants, of whom 2734 (74.5%) completed them all (Supplemental Figure 1). Of these, 2147 (78.5%) were at average risk, 450 (16.5%) were at higher than average risk, and 137 (5.0%) were at high risk. The follow-up question- naire was completed on average within 1 month after risk communication (mean = 25 days, SD = 36 days), whereas the 1-year follow-up questionnaire was completed on average 13 months after risk communication (mean = 395 days, SD = 47 days). Given that approximately a quarter of the initial study participants were excluded because of missing data over the course of the study, we examined whether attrition was related to the main study outcomes or other participant characteristics. Participants included in the analyses did not differ materially from those excluded in terms of baseline psychological distress (mean scores: 5.74 vs 5.43), breast cancer-related worries (mean scores: 6.65 vs 6.85), and age (means: 57.6 vs 58.6). However, the proportion of partici- pants excluded from the analyses was higher among those recruited in Ontario (35%) compared with Quebec (15%) and slightly different by risk level (average risk = 26%, higher than average risk = 22%, and high risk = 15%). The majority of participants determined to be at high risk were under the age of 60 (n = 137, 81.0%), had a first degree family history of breast cancer (n = 32, 64.2%), and were mainly from the province of Quebec (n = 105, 76.6%) (Table 1). Breast cancer worry and psychological distress The adjusted mean breast cancer worry and psychological distress scores before, at, and up to 1 year after risk communication are presented in Figures 1 and 2, respec- tively. Overall, the adjusted mean scores of breast cancer Table 1 Sociodemographic and health characteristics of 2734 participants who completed the 3 questionnaires Characteristics Risk Level TotalAverage Risk Higher Than Average Risk High Risk n = 2147 n = 450 n = 137 n = 2734 n (%)a n (%)a n (%)a n (%)a Age at risk assessment (y) Mean (SD) 58.3 (7.1) 55.9 (7.2) 52.1 (7.5) 57.6 (7.3) 40-49 272 (12.7) 90 (20.0) 54 (39.4) 416 (15.2) 50-59 849 (39.5) 192 (42.7) 57 (41.6) 1098 (40.2) 60-70 1026 (47.8) 168 (37.3) 26 (19.0) 1220 (44.6) Province Ontario 1101 (51.3) 190 (42.2) 32 (23.4) 1323 (48.4) Quebec 1046 (48.7) 260 (57.8) 105 (76.6) 1411 (51.6) Born in Canada Yes 1895 (88.6) 396 (88.4) 120 (88.2) 2411 (88.5) No 244 (11.4) 52 (11.6) 16 (11.8) 312 (11.5) Missing 8 2 1 11 Visible minority Not a visible minority 2009 (95.6) 409 (92.3) 126 (94.0) 2544 (95.0) Visible minority 93 (4.4) 34 (7.7) 8 (6.0) 135 (5.0) Don't know/prefer not to answer/missing 45 7 3 55 Highest level of education Below university bachelor’s degree 1049 (49.2) 212 (47.2) 47 (34.6) 1308 (48.1) University bachelor’s degree or above 1085 (50.8) 237 (52.8) 89 (65.4) 1411 (51.9) Prefer not to answer/missing 13 1 1 15 Marital status Married/common law 1638 (76.7) 336 (75.5) 103 (75.7) 2077 (76.5) Single/widowed/ divorced/ separated 497 (23.3) 109 (24.5) 33 (24.3) 639 (23.5) Prefer not to answer/missing 12 5 1 18 Employment status Employed 1252 (58.5) 286 (63.6) 106 (77.4) 1644 (60.3) Retired/not employed 888 (41.5) 164 (36.4) 31 (22.6) 1083 (39.7) Prefer not to answer/missing 7 0 0 7 Family history of breast cancer First- and second degree 124 (5.8) 91 (20.2) 56 (40.9) 271 (9.9) First degree only 264 (12.3) 97 (21.6) 32 (23.3) 393 (14.4) Second degree only 544 (25.3) 132 (29.3) 30 (21.9) 706 (25.8) None 1215 (56.6) 130 (28.9) 19 (13.9) 1364 (49.9) Number of previous mammograms 1 173 (11.5) 42 (13.0) 16 (15.4) 231 (11.9) 2-10 1109 (73.7) 225 (69.4) 72 (69.2) 1406 (72.8) 11-20 173 (11.5) 45 (13.9) 15 (14.4) 233 (12.1) >20 49 (3.3) 12 (3.7) 1 (1.0) 62 (3.2) Don’t know/missing 643 126 33 802 Age at first mammogram <40 300 (19.9) 99 (30.4) 46 (45.1) 445 (23.0) 40-49 614 (40.7) 146 (44.8) 42 (41.2) 802 (41.4) ≥50 595 (39.4) 81 (24.8) 14 (13.7) 690 (35.6) Don't know/missingb 638 124 35 797 Mammogram screening frequency before risk assessment Every year or less 413 (19.3) 149 (33.4) 60 (44.1) 622 (22.8) Every 2 or 3 years 1446 (67.6) 233 (52.2) 51 (37.5) 1730 (63.6) Do not have regular mammograms/had only 1 mammogram 281 (13.1) 64 (14.4) 25 (18.4) 370 (13.6) (continued) L. Lambert-Côté et al. 5 Table 1 Continued Characteristics Risk Level TotalAverage Risk Higher Than Average Risk High Risk n = 2147 n = 450 n = 137 n = 2734 n (%)a n (%)a n (%)a n (%)a Don’t know/missing 7 4 1 12 Perceived lifetime breast cancer risk before risk assessment Much lower than others 117 (5.7) 10 (2.4) 5 (3.7) 132 (5.0) Lower than others 474 (23.1) 67 (15.8) 18 (13.2) 559 (21.4) The same as others 1051 (51.3) 180 (42.4) 37 (27.2) 1268 (48.6) Higher than others 390 (19.0) 153 (36.1) 65 (47.8) 608 (23.3) Much higher than others 19 (0.9) 14 (3.3) 11 (8.1) 44 (1.7) Don’t know/missing 96 26 1 123 Overall health before risk assessment Excellent/very good 1443 (67.4) 311 (69.3) 110 (80.3) 1864 (68.3) Good 606 (28.3) 118 (26.3) 21 (15.3) 745 (27.3) Fair/poor 93 (4.3) 20 (4.4) 6 (4.4) 119 (4.4) Don’t know/missing 5 1 0 6 aPercentage excludes missing/prefer not to answer/don’t know. bIncludes those whose age at first mammogram was <20 years (n = 8). 6 L. Lambert-Côté et al. worry and psychological distress were low and remained so throughout the follow-up period, reaching a maximum of 7.1 out of a total score of 20 and 6.3 out of 40, respectively, at risk communication. The changes observed for these outcomes were small, with changes of less than 1 unit on the measurement scales. Adjusted mean breast cancer worry scores decreased slightly, although statistically significantly, at risk commu- nication in the average-risk group (P < .0001) and increased slightly in the high-risk group (P = .030) (Table 2). Worry about breast cancer decreased significantly between the period before risk assessment and 1 year after risk communication, both in the average-risk (P < .0001) and higher-than-average-risk (P = .008) groups, whereas no significant change was observed in the high-risk group (P = .211). Higher levels of breast cancer worry were observed among the high-risk group compared with the average- and higher-than-average-risk groups at risk communication and 1 year later, as well as in the trend observed before risk communication up to 1 year after disclosure (all P values < 0.05). Psychological distress increased slightly, although sta- tistically significantly, at risk level communication in the average (P < .0001) and higher-than-average-risk (P = .036) groups (Table 2). No significant difference was noted between risk levels for psychological distress at risk communication and 1 year later, as well as in the trend observed before risk communication up to 1 year post- disclosure. No statistically significant difference by risk level was observed for breast cancer worry and psychological distress, except for a slight increase in psychological distress over time in Ontario’s average-risk group compared with Que- bec’s (P = .008) (Supplemental Table 2). A sensitivity analysis was conducted, including the 925 excluded par- ticipants, and the results remained virtually unchanged. Factors associated with decisional regret Decisional regret 1 year after risk level communication was low, with a mean regret score of 10.9 out of 100 (SD = 13.5, median = 5.0), with 46.8% of participants reporting no regret at all about their decision (score = 0). Factors asso- ciated with decisional regret 1 year after risk level communication are presented in Table 3. In the multivari- able analysis, for those at high risk, having a family history of breast cancer was associated with a higher decisional regret score than for participants at average risk with no family history (P = .001). In contrast, the absence of family history for women at higher than average risk was associ- ated with a higher decisional regret (P = .003). Women who perceived their breast cancer risk as much higher/higher than others before risk assessment had a lower decisional regret score than those who perceived their risk as the same as others (P < .0001). Decisional regret was higher among members of visible minorities (P = .041). Of participants who decided to follow the proposed screening action plan, those who reported changes in their usual screening expe- rienced less regret 1 year after risk disclosure than those who reported no change in their usual screening (P = .009). Participants who felt relief after risk disclosure had lower Figure 1 Adjusted mean score for breast cancer worry before and after risk communication by risk level (n = 2522). aAdjusted for age group, province, education, visible minority status, family history of breast cancer, perceived risk, and psychological distress. L. Lambert-Côté et al. 7 decisional regret scores than those who had no relief at all (P < .0001). Finally, a higher satisfaction score with the in- formation received was associated with a lower decisional regret score (P < .0001). 5.74 5.87 5.37 0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 Ad ju st ed m ea n sc or ea Average n=1938/2147 Higher than average n=406/450 High n=132/137 30.00 40.00 Figure 2 Adjusted mean score for psychological distress before and age group, province, education, visible minority status, family history o Emotional outcome of knowing risk level 1 year after risk communication, most participants reported some degree of relief about knowing their breast cancer risk 6.23 6.02 6.31 6.09 5.49 5.72 after risk communication by risk level (n = 2476). aAdjusted for f breast cancer, perceived risk, and worry about breast cancer. Table 2 Differences in adjusted mean score for breast cancer worry and psychological distress over time by risk level Variable Time Risk Level Adjusted Meana (95% CI) P value Breast cancer worry (n = 2522) At risk vs before risk communication Average −0.21 (−0.28 to −0.15) <.0001 Higher than average −0.01 (−0.18 to 0.15) .859 High 0.38 (0.04-0.71) .030 1 year after risk vs at risk communication Average −0.13 (−0.19 to −0.07) <.0001 Higher than average −0.22 (−0.38 to −0.06) .008 High −0.18 (−0.52 to 0.16) .296 At risk communication Average vs higher than average −0.24 (−0.44 to −0.05) .015 Average vs high −0.66 (−1.00 to −0.31) <.001 Higher than average vs high −0.41 (−0.79 to −0.04) .032 1 year after risk communication Average vs higher than average −0.16 (−0.34 to 0.02) .086 Average vs high −0.61 (−0.96 to −0.27) .001 Higher than average vs high −0.45 (−0.82 to −0.08) .017 Before risk up to 1 year after risk communication Average −0.17 (−0.21 to −0.14) <.0001 Higher than average −0.12 (−0.20 to −0.03) .008 High 0.10 (−0.06 to 0.25) .211 Average vs higher than average −0.06 (−0.15 to 0.04) .228 Average vs high −0.27 (−0.43 to −0.12) .001 Higher than average vs high −0.21 (−0.39 to −0.04) .017 Psychological distress (n = 2476) At risk vs before risk communication Average 0.48 (0.30-0.67) <.0001 Higher than average 0.43 (0.03-0.84) .036 High 0.12 (−0.58 to 0.83) .729 1 year after risk vs at risk communication Average −0.21 (−0.40 to −0.02) .030 Higher than average −0.22 (−0.67 to 0.23) .340 High 0.23 (−0.48 to 0.93) .527 At risk communication Average vs higher than average −0.08 (−0.65 to 0.50) .787 Average vs high 0.74 (−0.14 to 1.61) .100 Higher than average vs high 0.82 (−0.15 to 1.78) .099 1 year after risk communication Average vs higher than average −0.07 (−0.67 to 0.53) .820 Average vs high 0.30 (−0.59 to 1.19) .509 Higher than average vs high 0.37 (−0.63 to 1.37) .468 Before risk up to 1 year after risk communication Average 0.14 (0.04 to 0.24) .007 Higher than average 0.11 (−0.13 to 0.35) .376 High 0.18 (−0.23 to 0.58) .396 Average vs higher than average 0.03 (−0.23 to 0.29) .827 Average vs high −0.04 (−0.46 to 0.38) .856 Higher than average vs high −0.07 (−0.54 to 0.40) .779 aAdjusted for age group, province, education, visible minority, family history of breast cancer, perceived risk and worry about breast cancer, or psy- chological distress. 8 L. Lambert-Côté et al. level (79.9%) and were not upset at all (81.4%) (Figure 3). Regardless of their family history of breast cancer, fewer participants at higher than average risk and at high risk were relieved (all P values < .005), and more participants were upset compared with women at average risk without a family history of breast cancer (all P values < .0001) (Supplemental Table 3). Discussion In this study, which evaluated the impact of communicating personal breast cancer risk levels up to 1 year after risk disclosure, there was no evidence of major adverse impact on breast cancer worry and psychological distress. Overall, most participants were somewhat relieved and not upset at all to learn about their breast cancer risk level, but this varied depending on their risk levels. Decisional regret 1 year after risk level communication was low, and almost half of the participants expressed no regret at all. Certain characteristics were associated with lower levels of decisional regret, including perceiving lifetime risk before risk communication as much higher or higher than others, willingness to follow proposed screening action plan with changes to usual breast screening, degree of relief after risk disclosure, and higher satisfaction with the information received. Inversely, deci- sional regret was higher among members of visible minorities. In the multivariable analysis, for those at high risk, having a family history of breast cancer was associated with a higher decisional regret score than for participants at average risk with no family history (P = .001). In contrast, the absence of family history for women at higher-than- average risk was associated with a higher decisional regret (P = .003). Table 3 Factors associated with decisional regret mean scores 1 year after risk level communication Characteristics n Univariate Multivariate Mean Score (SE) P Valuea Adjusted Mean Score (SE) P Valuea Total (SD) 2638 10.93 (13.46) Risk Level Average 2066 10.26 (0.29) Higher than average 437 13.46 (0.64) <.0001 High 135 12.95 (1.15) .024 Age group at risk assessment (y) 40-49 410 9.88 (0.66) .085 9.38 (0.68) .113 50-59 1064 11.22 (0.41) 10.64 (0.39) 60-70 1164 11.03 (0.39) .732 10.49 (0.39) .787 Family history of breast cancer No 1309 11.05 (0.37) Yes 1329 10.81 (0.37) .636 Risk level and family history Average risk without FHx 1164 10.43 (0.39) 9.94 (0.41) Average risk with FHx 902 10.04 (0.45) .505 10.05 (0.44) .865 Higher than average risk without FHx 126 16.50 (1.19) <.0001 13.87 (1.25) .003 Higher than average risk with FHx 311 12.23 (0.76) .036 9.98 (0.80) .972 High risk without FHx 19 12.89 (3.07) .426 11.28 (2.98) .657 High risk with FHx 116 12.96 (1.24) .052 14.60 (1.40) .001 Province Ontario 1257 10.92 (0.38) 9.79 (0.39) Quebec 1381 10.93 (0.36) .989 10.87 (0.36) .058 Highest level of education Below bachelor’s degree 1253 11.37 (0.38) Bachelor’s degree or above 1372 10.51 (0.36) .103 Marital status Single/widowed/ divorced/ separated 617 10.80 (0.54) Married/common law 2004 10.91 (0.30) .859 Employment status Employed 1592 10.82 (0.34) Retired/not employed 1040 11.09 (0.42) .610 Visible minority group membership Not a visible minority 2461 10.60 (0.27) 10.26 (0.25) Visible minority 125 15.65 (1.19) <.0001 12.89 (1.26) .041 Perceived lifetime breast cancer risk before risk assessment Much lower/lower than others 664 11.44 (0.52) .526 11.51 (0.51) .298 The same as others 1225 11.03 (0.38) 10.87 (0.36) Much higher/higher than others 639 9.75 (0.53) .051 8.23 (0.54) <.0001 Age at first mammogram <50 1208 10.49 (0.39) .294 ≥50 666 11.17 (0.52) Don’t know/missingb 764 11.41 (0.49) .736 Mammogram screening frequency before risk assessment Every year or less 596 11.56 (0.55) .270 Every 2 or 3 years 1665 10.85 (0.33) Do not have regular mammograms/ had only one mammogram 365 10.22 (0.70) .413 Overall health .542 Excellent/very good 1801 10.79 (0.32) .631 Good 713 11.07 (0.50) Fair/poor 118 12.13 (1.24) .429 (continued) L. Lambert-Côté et al. 9 Table 3 Continued Characteristics n Univariate Multivariate Mean Score (SE) P Valuea Adjusted Mean Score (SE) P Valuea Risk level discussed with HCP Yes 1860 11.01 (0.31) No 758 10.83 (0.49) .749 Decision-making score 735 0.46c (0.13) <.001 Decision to follow breast screening action plan Yes, there were no changes to my usual screening 1739 10.04 (0.32) 10.49 (0.31) Yes, will follow changes to my usual screening 413 10.08 (0.65) .958 8.52 (0.66) .009 No, will not follow screening action plan/health care professional has not recommended it/due to COVID-19 187 14.44 (0.97) <.0001 11.86 (0.94) .170 Don’t know 262 15.14 (0.82) <.0001 11.59 (0.85) .227 Degree of relief after risk disclosure No relief at all 504 15.41 (0.58) 13.47 (0.63) Slight/moderate/considerable relief 1999 9.38 (0.29) <.0001 9.59 (0.29) <.0001 Degree of upset after risk disclosure Not upset at all 2083 9.88 (0.29) Slightly/moderately/very upset 472 14.05 (0.60) <.0001 Satisfaction with the information received 2612 1.40c (0.08) <.0001 −1.31a (0.08) <.0001 Psychological distress before risk assessment 2636 0.12c (0.05) .024 Breast cancer worry before risk assessment 2632 0.42c (0.15) .005 FHx, Family history of breast cancer; HCP, health care professional. aP value of the mean difference. bIncludes those whose age at first mammogram was <20 years (n = 8). cEstimate from the linear regression. 10 L. Lambert-Côté et al. Our study showed that the emotional outcomes after risk communication and breast cancer worry changed in line with the risk levels provided. For instance, regardless of family history, being identified at higher-than-average or high risk was associated with experiencing less relief and being more upset 1 year after risk disclosure. Higher levels of breast cancer worry were observed over time in the high- risk group compared with the average- and higher-than- average-risk groups. This is consistent with findings from the PROCAS 2 study (Breast Cancer Predict), in which breast cancer worry changed in line with the risk levels provided (high, moderate, average, and below average) 6 months after risk disclosure.14 Despite statistically signifi- cant differences between risk groups in our study, the dif- ferences observed on the breast cancer worry scale were very small and unlikely to be clinically significant. There- fore, our findings suggest that concerns that risk stratifica- tion would produce adverse psychological effects through increased breast cancer worry or anxiety are not supported, even for individuals identified at high risk. This is consistent with previous studies indicating that communicating risk levels may have no or limited effect on breast cancer anx- iety, far from reaching clinical levels.12-14 However, it should be kept in mind that even small individual differ- ences, even if not significant enough to be considered pathological, can have meaningful effects when aggregated across a population. During follow-up, no significant difference was observed between risk levels for psychological distress. Levels of psychological distress in this study (Mean K10 score = 5.7/ 40, SD = 5.1) were also comparable to those observed in the Canadian general population (Mean K10 score = 5.4/40, SD = 5.5).30 Decisional regret 1 year after risk level communication was also very low in our study (Mean = 10.9/100, SD = 13.5, Median = 5.0). This is similar to the decisional regret observed among women who received their breast cancer PRS (Mean = 9.3/100, SD = 15.1).11 Our study shows that decisional regret 1 year after risk communication among women aged 40 to 49 does not differ from that in women aged 50 to 59. This is an encouraging result for potentially including participants 40 to 49 in screening pro- grams, a target many jurisdictions are moving toward. Figure 3 Emotional impacts from learning breast cancer risk level 1 year after risk communication (n = 2734). A. Excludes don’t know/missing data (n = 153). B. Excludes don’t know/missing data (n = 98). L. Lambert-Côté et al. 11 Study strengths and limitations This study has several strengths. First, the participation rate in both follow-up questionnaires was excellent, resulting in a large sample size. Second, our study assessed the impacts across all 3 risk levels, which is crucial for understanding how risk communication may affect diverse risk groups. If implemented at the population level, risk-stratified breast cancer screening will be available to all eligible individuals, with screening frequency and modalities tailored according to each woman’s risk category. Third, our study assessed decisional regret, an important factor to consider when implementing a risk-based screening approach within existing screening programs because it may affect future engagement. Fourth, participants were followed up to 1 year after risk disclosure, providing a longer-term perspective on the impact of risk level communication compared with other studies at a population level. The results should be interpreted with consideration of the potential limitations. First, approximately 15% of our cohort was 40 to 49 years of age and had a mammogram. Therefore, they may have already known/suspected that they had an increased risk of breast cancer because this age group was not targeted by either province’s breast screening program at the time of the study. Second, compared with the Canadian census, a greater proportion of PERSPECTIVE 12 L. Lambert-Côté et al. I&I participants were not visible minorities and had a higher educational attainment.9 Third, in Quebec, participants were also required to have a primary HCP to whom the risk letter was systematically sent. According to a 2022 survey, it is estimated that more than 1 in 5 Canadians do not have a family physician or nurse practitioner they see regularly.31 Consequently, access to information and guidance about the personalized screening action plan, as well as referral for recommended screening exams, would be a key issue at the population level. Fourth, the indicators used in this study are specific indicators that do not take into account all aspects related to the psychological and emotional outcomes. For all of these reasons, it is likely that the psychological and emotional burden maybe greater in the general population. Considerations for implementation Our results underline the importance of having risk communication strategies that consider the specific emotional needs of individuals, particularly those who will be identified at higher levels of risk. Risk communication should also include comprehensive and clear information tools for participants. In this study, higher satisfaction with the received information was associated with a lower deci- sional regret score 1 year after risk disclosure. A systematic review reported that lower satisfaction with the information provided was significantly associated with greater regret about health decisions in some studies,32 which is consistent with our findings. This systematic review also reported that belonging to a minority race/ethnicity was associated with decisional regret, consistent with our study results.32 Having culturally appropriate breast screening information at the population level is crucial for improving health outcomes, reducing disparities, and reducing decisional regret. In this study, participants who perceived their risk as “much higher/higher than others” before risk assessment experienced less decisional regret than those who perceived their risk as “the same as other,” which suggests that risk perception before risk assessment could be an important factor in determining future reactions of individuals after risk communication. As highlighted in a systematic review of qualitative research, women have preconceptions and expectations about their breast cancer risk before receiving a clinical risk estimate.33 The results could inform participants that their risk is lower than expected or validate their risk appraisals. In the first case, this is consistent with our findings that feeling relieved in some way after risk communication is associated with less regret about the de- cision. In the latter, confirming a higher risk could be ad- vantageous, potentially allowing access to more frequent mammograms or magnetic resonance images. This is in line with our findings, which indicate that changes to the screening action plan were associated with less decisional regret. Screening for high-penetrance pathogenic variants in susceptibility genes, such as BRCA1, BRCA2, and PALB2, was not performed in our study. This could have increased decisional regret among some women. Greater decisional regret was observed in our study among high-risk women with a family history of breast cancer. How individuals would be recruited for breast cancer risk-stratified screening at the population level could have an impact on emotional outcomes after risk communica- tion. Participants from Quebec reported being less relieved from learning their risk level than participants from Ontario, which could be partially explained by the differ- ence in the recruitment method. Ontario’s sample was recruited via a population-based mail invitation approach from the provincial screening program, whereas Quebec participants were convenience-sampled, and interested women registered on our study website. With this latter approach, it is likely that individuals with stronger contributory risk factors participated. For example, Quebec participants were much more likely than Ontario partici- pants to have a family history of breast cancer (first and/or second degree).9 Seeking validation of being at high risk may have motivated some women to participate in the study, as previously observed in other studies.33 Motiva- tions and expectations to enroll in a risk-stratified study could lead to different emotional outcomes, which should be considered when implementing such an approach within a screening program. In conclusion, our observations suggest that there is no evidence ofmajor adverse psychological outcomes associated with personalized breast cancer risk communication. It also highlights some considerations for implementing a risk- stratified breast cancer screening approach at the population level. Further research should examine the other implications of risk stratification, particularly how women and their HCPs can use information on risk level and the associated screening action plan to make informed decisions about breast cancer screening, as well as the clinical outcomes. It will be essential to assess the readiness of healthcare organizations and determine the best approaches for implementation. Data Availability Parts of the material underlying this article are based on data and information provided by Ontario Health (Cancer Care Ontario). Ontario Health is prohibited from making the data used in this research publicly accessible if they include potentially identifiable personal health information and/or personal information as defined in Ontario law, specifically the Personal Health Information Protection Act and the Freedom of Information and Protection of Privacy Act. Upon request, data deidentified to a level suitable for public release may be provided. A subset of the Quebec partici- pants have consented to sharing their data in the context of future research. Deidentified data from these participants are available upon request to the principal investigator L. Lambert-Côté et al. 13 of the PERSPECTIVE I&I project (jacques.simard@ crchudequebec.ulaval.ca). For the other subset of Quebec participants, data cannot be shared because of consent form constraints. No personally identifiable information will be shared. Acknowledgments The authors thank and acknowledge the PERSPECTIVE I&I Activity 3 Project Team (alphabetical): Lucie Amyot, Gabriel Couture, Gratien Dalpé, Martine Dumont, Clarissa Encisa, Hortense Galois, Palmira Granados, Julie Lapointe, Emmanuelle Lévesque, Cynthia MBuya-Bienge, Penny Soucy, Rosemary Sousa, and Lara Tardif-Michaud; collab- orators and health professionals: Nathalie Bolduc, Vivianne Freitas, and Kardi Kennedy; Ontario Health: Andrea Mackesy and Emma Sabo; and PULSAR and Université Laval: Kevin Arseneault, François Breton, Anne-Sylvie Chenat, Marie-Noëlle Guillemette, Marie-Andrée Lev- esque, Jean-Philippe Lévesque, and Sylvain Parent. Funding This work was supported by the Government of Canada through Genome Canada (grant #: 13529), the Canadian Institutes of Health Research (grant #: 155865), the Minis- tère de l’Économie et de l’Innovation du Québec through Génome Québec, the Quebec Breast Cancer Foundation, the CHU de Québec Foundation, the CHU de Québec-Uni- versité Laval Research Center, and the Ontario Ministry of Research and Innovation through the Ontario Research Fund. Antonis C. Antoniou and Tim Carver are supported by Cancer Research UK grant: PPRPGM-Nov20\100002. Author Contributions Conceptualization: A.C.A., J.D.B., J.C., D.F.E., A.E., L.E., Y.J., B.M.K.,H.N.,N.P.,M.J.W.,A.M.C., J.S.,M.D.; Formal Analysis: L.L.-C., A.T., E.D., A.M.C., J.S., M.D.; Funding Acquisition: A.M.C, J.S.; Investigation: L.L.-C., A.T., K.M.B., A.C., A.C.A., T.C., S.-L.C., D.F.E., C.L.C., J.L.; Project Administration: L.L.-C., A.T., K.M.B., A.C.; Re- sources: L.L.-C.,A.T.,K.M.B.,A.C., K.A.B., J.C., A.E., S.F., R.H.K., J.L., A.L., J.-S.P., A.J.S., T.L.S., A.M.C., J.S., M.D.; Writing-original draft: L.L.-C., A.T., K.M.B., A.C., A.C.A., K.A.B., M.J.M.B., J.D.B., T.C., S.-L.C.; J.C., E.D., D.F.E., A.E., L.E., D.G.R.E., S.F.,Y.J., R.H.K., B.M.K., C.L.-C., J.L., A.L., H.N., J.-S.P., N.P., A.J.S., T.L.S., M.J.W., A.M.C., J.S., M.D.; Writing-review and editing: L.L.-C., A.T., K.M.B., A.C., A.C.A., K.A.B., M.J.M.B., J.D.B., T.C., S.-L.C.; J.C., E.D., D.F.E., A.E., L.E., D.G.R.E., S.F.,Y.J., R.H.K., B.M.K., C.L.-C., J.L., A.L., H.N., J.-S.P., N.P., A.J.S., T.L.S., M.J.W., A.M.C., J.S., M.D. Ethics Declaration The study was approved by the Ethics Research Committees of the CHU de Québec-Université Laval (MP-20-2020- 4670), McGill University (A12-B65-18A), University of Toronto (00036881), Grand River Hospital (2020-0709), McMaster University (11468), St. Michael’s Hospital (19- 220), Sunnybrook Health Sciences Centre (2255), Univer- sity Health Network (19-5340), and Queens University (6030732 EPID-712-20). Informed consent was obtained from all participants involved in the study. Conflict of Interest Antonis C. Antoniou, Tim Carver, and Douglas F. Easton are creators of BOADICEA, which has been licensed to Cambridge Enterprise (University of Cambridge). The fun- ders had no role in the design of the study; collection, an- alyses or interpretation of data; writing of the manuscript; or decision to publish the results. All other authors declare no conflicts of interest. Additional Information The online version of this article (https://doi.org/10.1016/j. gim.2025.101453) contains supplemental material, which is available to authorized users. Affiliations 1CHU de Québec-Université Laval Research Center, Quebec City, QC, Canada; 2Ontario Health, Toronto, ON, Canada; 3Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; 4IQ Health Science Department, Radboud university medical center, Nijmegen, The Netherlands; 5Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; 6Centre des maladies du sein, CHU de Québec-Université laval, Quebec City, QC, Canada; 7Department of Family Medicine and Emergency Medicine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada; 8Sunnybrook Health Science Centre, Toronto, ON, Canada; 9Programme québécois de cancérologie, Ministère de la Santé et des Services sociaux, Quebec City, QC, Canada; 10Centre intégré de santé et de services sociaux de Lanaudière, Joli- ette, QC, Canada; 11Department of Medical Genetics and Cancer Epidemiology, The University of Manchester, Manchester, United Kingdom; 12Centre of Genomics and Policy, McGill University, Montreal, QC, Canada; 13Prin- cess Margaret Cancer Centre, Toronto, ON, Canada; 14Canada Women’s College Research Institute, Toronto, mailto:jacques.simard@crchudequebec.ulaval.ca mailto:jacques.simard@crchudequebec.ulaval.ca https://doi.org/10.1016/j.gim.2025.101453 https://doi.org/10.1016/j.gim.2025.101453 14 L. Lambert-Côté et al. ON, Canada; 15Department of Social and Preventive Med- icine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada; 16Université Laval Cancer Research Center, Quebec City, QC, Canada; 17Division of Clinical Labora- tory Genetics, University Health Network, Toronto, ON, Canada; 18Department of Laboratory Medicine and Patho- biology, University of Toronto, Toronto, ON, Canada; 19Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada; 20Faculty of Pharmacy, Université Laval, Quebec City, QC, Canada References 1. Dibden A, Offman J, Duffy SW, Gabe R. Worldwide review and meta-analysis of cohort studies measuring the effect of mammography screening programmes on incidence-based breast cancer mortality. Cancers (Basel). 2020;12(4):976. http://doi.org/10.3390/cancers12040 976 2. Esserman LJ, WISDOM Study, Investigators Athena. 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Br J Cancer. 2022;127(11):1916-1924. http://doi.org/10. 1038/s41416-022-01944-x http://doi.org/10.1016/j.ssmph.2023.101414 http://doi.org/10.1503/cmaj.1096049 http://doi.org/10.1503/cmaj.1096049 http://doi.org/10.1177/0272989X16636113 http://doi.org/10.1177/0272989X16636113 http://doi.org/10.1038/s41416-022-01944-x http://doi.org/10.1038/s41416-022-01944-x Psychological and emotional impacts of communicating breast cancer risk using multifactorial assessment with polygenic risk ... Introduction Materials and Methods Context Participants Data collection Measures Breast cancer worry Psychological distress Regret after the decision to know the level of risk Information on follow-up with the health care providers, the intention to follow the screening action plan, and satisfactio ... Emotional outcomes of knowing risk level Sociodemographic and health information Data analysis Results Breast cancer worry and psychological distress Factors associated with decisional regret Emotional outcome of knowing risk level Discussion Study strengths and limitations Considerations for implementation Data Availability Acknowledgments Funding Author Contributions Ethics Declaration Conflict of Interest Additional Information References